Process for the preparation of a metal salt of clavulanic acid

Abstract

A process for the preparation of a metal salt of clavulanic acid which comprises the reaction between an organic amine salt of clavulanic acid and a metal salt precursor compound, the reaction taking place in a liquid medium which comprises a liquid florinated and/or chlorinated hydrocarbon.

What is claimed is:  
     
       1. A process for the preparation of a metal salt of clavulanic acid which comprises the reaction between an organic amine salt of clavulanic acid and a metal salt precursor compound, the reaction taking place in a liquid medium which comprises a liquid fluorinated and/or chlorinated hydrocarbon. 
     
     
       2. A process according to claim  1 , characterised in that the organic amine salt of clavulanic acid is the salt of clavulanic acid with tertiary-butylamine, a N,N′-substituted diamine, an N,N′-monosubstituted symmetric diamines or N,N′-monosubstituted symmetric alkylethylene diamine or tertiary octylamine. 
     
     
       3. A process according to claim  1 , characterised in that the metal salt precursor compound is a salt or salt-like compound, or a basic compound, of a metal cation with a counter anion. 
     
     
       4. A process according to claim  3  characterised in that the metal in the metal salt precursor compound is potassium or sodium. 
     
     
       5. A process according to claim  4  characterised in that the metal salt precursor compound is a salt of the metal with an organic carboxylic acid of formula (I): 
       
         
           R 10 —CO 2 H  (I)  
         
       
       wherein R 10  is an alkyl group containing from 1 to 20 carbon atoms. 
     
     
       6. A process according to claim  5  characterised in that the metal salt precursor compound is potassium 2-ethylhexanoate. 
     
     
       7. A process according to claim  1  characterised in that the liquid medium is a gas at ambient temperature which can be liquefied at ambient temperature by pressure. 
     
     
       8. A process according to claim  7  characterised in that the boiling point for the liquid fluorinated and/or chlorinated hydrocarbon is −10 to −50° C. at ambient atmospheric pressure. 
     
     
       9. A process according to claim  1  characterised in that the fluorinated and/or chlorinated hydrocarbon is a compound of formula CnHmXpYr where X is fluorine, Y is chlorine n and m are whole numbers, p and r are zero or whole numbers provided both p and r are not zero and (m+p+r) equals 2n+2. 
     
     
       10. A process according to claim  1  characterised in that the liquid medium is a fluorinated non-chlorinated hydrocarbon. 
     
     
       11. A process according to claim  9  characterised in that the medium is a fluorinated non-chlorinated compound of formula C n H m F p  where n, m and p are whole numbers and (m+p) equals 2n+2. 
     
     
       12. A process according to claim  11  characterised in that n is 2 or 3. 
     
     
       13. A process according to claim  1  characterised in that the fluorinated and/or chlorinated hydrocarbon is selected from 1,1,1,2-tetrafluoroethane, fluoroform, methyl chloride, difluorodichloromethane, monofluoromethane, difluoromethane, trifluoromethane, pentafluoroethane, 1,1,1-trifluoroethane, 1,1-difluoroethane, 1,1,1,2,3,3,3-heptafluoropropane, 1,1,1,2,2,3,3-heptafluoropropane, 1,1,1,3,3,3-hexafluoropropane, 1,1,1,2,2-pentafluoropropane, 1,1,1,2,2,3-hexafluoropropane, 1,1,2,2,3,3-hexafluoropropane, and 1,1,1,2,3,3-hexafluoropropane. 
     
     
       14. A process according to claim  1  characterised in that the liquid medium comprises a mixture of fluorinated and/or chlorinated hydrocarbons. 
     
     
       15. A process according to claim  1  characterised in that the metal salt of clavulanic acid prepared in the reaction is potassium clavulanate.